Medicinal Chemistry Research

, Volume 16, Issue 3, pp 101–111 | Cite as

Substituted aminoalcohol ester analogs of indomethacin with reduced toxic effects

  • Parmeshwari K. Halen
  • Kewal K. Chagti
  • Rajani Giridhar
  • Mange Ram YadavEmail author
Original Research


Synthesis and evaluation of five different N,N-disubstituted aminoethanol ester derivatives of indomethacin bearing structural resemblance to the aminoethanol ester class of anticholinergics are reported herein. The anticholinergic activity was incorporated into the intact esters to overcome the gastric toxicity of indomethacin, not only by blocking the acidic functionality but also by decreasing gastric secretions and motility. These derivatives exhibited in vitro stability in buffers of pH 2.0 and 7.4 for 6 h and were readily hydrolyzed by human plasma esterases to liberate the parent drug. All the derivatives were significantly less irritating to the gastric mucosa than the parent drug. Though only two esters showed antiinflammatory activity similar to that of the parent drug at equivalent dose levels, all the esters were equipotent to indomethacin in the mouse acetic acid–induced writhing assay for analgesic action. The present evaluation indicates that the combined pharmacological properties of these ester derivatives may prove useful for design and development of novel gastric sparing antiinflammatory molecules with potentially important therapeutic applications.


Antiinflammatory Indomethacin Ulceration 


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The authors thank AICTE (All India Council of Technical Education), New Delhi for providing financial support through a research grant (TAPTEC Major Research Project).


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Copyright information

© Birkha¨user Boston 2007

Authors and Affiliations

  • Parmeshwari K. Halen
    • 1
  • Kewal K. Chagti
    • 1
  • Rajani Giridhar
    • 1
  • Mange Ram Yadav
    • 1
    Email author
  1. 1.Pharmacy Department, Faculty of Technology and Engineering, KalabhavanThe M.S. University of BarodaVadodaraIndia

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